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Objective: We aimed to better understand the challenges related to type 2 diabetes medication-taking through Theoretical Domains Framework (TDF)-guided interviews with people with type 2 diabetes with varying degrees of medication-taking. Methods: One-on-one qualitative interviews following a semistructured discussion guide informed by the TDF were conducted. Thirty people with type 2 diabetes in Canada were interviewed, with representation from across the country, of both sexes (47% female), of people with various diabetes durations (mean 12.9 ± 7.9 years), with different types of medication plans (n = 15 on polypharmacy), and with various medication-taking levels (n = 10 each for low-, medium-, and high-engagement groups). Results: Themes related to medication-taking from interviews mapped to 12 of the 14 TDF theme domains, with the exclusion of the knowledge and skills domains. The most prominent domains, as determined by high-frequency themes or themes for which people with low and high medication-taking had contrasting perspectives, were 1) emotion; 2) memory, attention, and decision processes; 3) behavioral regulation; 4) beliefs about consequences; 5) goals; and 6) environmental context and resources. Conclusion: Through our interviews, several areas of focus emerged that may help efforts to increase medication-taking. To validate these findings, future quantitative research is warranted to help support people with type 2 diabetes in overcoming psychological and behavioral barriers to medication-taking.
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AIMS: The objectives of this scoping review were to: (1) identify the target audience and contexts in which strategies to improve type 2 diabetes mellitus (T2DM) medication adherence have been used, (2) provide an overview of behaviour change techniques (BCTs) used, (3) describe the determinants of behaviour targeted by strategies and (4) to identify current gaps in strategies. METHODS: A systemic search for articles related to T2DM, medication adherence and strategies was conducted in EMBASE, Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily using the OvidSP platform on 11 March 2021. All publications involving strategies to overcome medication non-adherence among adults with T2DM were included. Strategies were categorized according to the BCT taxonomy and the determinants of behaviour targeted by each strategy were classified by using the Theoretical Domains Framework (TDF). RESULTS: The search identified 58 articles and 61 strategies. The BCT categories Antecedents and Natural consequences and BCTs Feedback on outcome(s) of behaviour, Adding objects to the environment and Information about health consequences were identified most frequently as components of strategies resulting in statistically significant improvement in medication adherence. Strategies targeting the TDF domains Reinforcement and Beliefs about Consequences most often resulted in statistically significant improvements in adherence measures. CONCLUSIONS: The findings from this review identify BCTs and targeted behaviours with demonstrated success. Further exploration of the myriad of BCTs and the corresponding determinants of behaviour which were not accessed may be warranted for the development of future strategies to improve medication adherence in type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Adesão à Medicação , Terapia Comportamental/métodosRESUMO
Pancreatic islet transplantation has therapeutic potential in type 1 diabetes and is also an established therapy in chronic pancreatitis. However, the long-term transplant outcomes are modest. Identifying indicators of graft function will aid the preservation of transplanted islets and glycemic control. We analyzed beta cell prohormone peptide levels in a retrospective cohort of total pancreatectomy autologous islet transplant patients (n = 28). Proinsulin-to-C-peptide (PI/C) and proIAPP-to-total IAPP (proIAPP/IAPP) ratios measured at 3 months post-transplant were significantly higher in patients who remained insulin dependent at 1 year follow-up. In an immuno-deficient mouse model of human islet transplantation, recipient mice that later became hyperglycemic displayed significantly higher PI/C ratios than mice that remained normoglycemic. Histological analysis of islet grafts showed reduced proportional insulin- and proinsulin-positive area, but elevated glucagon-positive area in grafts that experienced greater secretory demand. Increased prohormone convertase 1/3 was detected in glucagon-positive cells, and glucagon-like peptide 1 (GLP-1) area was elevated in grafts from mice that displayed hyperglycemia or elevated plasma PI/C ratios, demonstrating intra-islet incretin production in metabolically challenged human islet grafts. These data indicate that in failing grafts, alpha cell prohormone processing is likely altered, and incomplete beta cell prohormone processing may be an early indicator of insulin dependency.
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Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Animais , Peptídeo C , Glucagon , Humanos , Insulina , Camundongos , Proinsulina , Estudos RetrospectivosRESUMO
AIM: To investigate once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D) in routine clinical practice. METHODS: The SURE Canada study was a multicenter, prospective, observational study. Adults with T2D and one or more documented HbA1c values 12 weeks or less before semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~30 weeks). Secondary endpoints included change in body weight (BW), waist circumference and patient-reported outcomes (PROs) and the proportion of patients achieving HbA1c of less than 7.0%, weight loss (WL) of 5% or higher, and a composite of HbA1c reduction of 1% or higher and WL of 3% or higher at EOS. Data were analysed and presented for patients on semaglutide at EOS overall and for the following baseline medication subgroups: oral antihyperglycaemic drugs (OADs) only; GLP-1RA experienced; insulin ± OADs without GLP-1RA. RESULTS: In total, 452 patients initiated semaglutide and 356 completed the study on treatment. For the 452 patients, mean baseline HbA1c was 8.1%; 86 (19.0%) patients had HbA1c of less than 7.0%. Mean dose of semaglutide at EOS was 0.76 ± 0.31 mg. Mean HbA1c was reduced by 0.9%-point (95% confidence interval [CI]: 0.97; 0.78). Mean BW was reduced by 4.3 kg (95% CI: 4.79; 3.76). At EOS, 46.9% of patients achieved HbA1c of less than 7.0%, 40.9% achieved WL of 5% or higher and 24.1% achieved the composite endpoint. PROs improved from baseline to EOS. No new safety concerns were reported. CONCLUSIONS: In SURE Canada, patients treated with OW semaglutide in routine clinical practice experienced clinically significant improvements in HbA1c, BW and other outcomes, supporting semaglutide use in routine clinical practice.
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Diabetes Mellitus Tipo 2 , Adulto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes , Estudos ProspectivosRESUMO
Context: Islet amyloid is a feature of ß-cell failure in type 2 diabetes (T2D) and type 1 diabetes (T1D) recipients of islet transplants. Islet amyloid contains islet amyloid polypeptide (IAPP; amylin), a circulating peptide that is produced in ß cells by processing of its precursor, proIAPP1-67, via an intermediate form, proIAPP1-48. Elevated proinsulin to C-peptide ratios in the plasma of persons with diabetes suggest defects in ß-cell prohormone processing. Objective: Determine whether plasma levels of precursor forms of IAPP are elevated in diabetes. Design, Setting, and Patients: We developed an immunoassay to detect proIAPP1-48 in human plasma, and we determined the ratio of proIAPP1-48 to mature IAPP in subjects with T1D, T2D, recipients of islet transplants, and healthy controls. Results: The proIAPP1-48 immunoassay had a limit of detection of 0.18 ± 0.06 pM and cross-reactivity with intact proIAPP1-67 <15%. Healthy individuals had plasma concentrations of proIAPP1-48 immunoreactivity of 1.5 ± 0.2 pM and a proIAPP1-48 to total IAPP ratio of 0.28 ± 0.03. Plasma concentrations of proIAPP1-48 immunoreactivity were not significantly different in subjects with T2D but were markedly increased in T1D recipients of islet transplants. Children and adults with T1D had reduced mature IAPP levels relative to age-matched controls but an elevated ratio of proIAPP1-48 to total IAPP. Conclusion: The ß cells in T1D and islet transplants have impaired processing of the proIAPP1-48 intermediate. The ratio of proIAPP1-48-to-IAPP immunoreactivity may have value as a biomarker of ß-cell stress and dysfunction.
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Amiloide/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Polipeptídeo Amiloide das Ilhotas Pancreáticas/sangue , Transplante das Ilhotas Pancreáticas , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/cirurgia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/cirurgia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Proinsulina/metabolismo , Valores de Referência , Medição de RiscoRESUMO
ß-Cell replacement by islet transplantation is a potential curative therapy for type 1 diabetes. Despite advancements in islet procurement and immune suppression that have increased islet transplant survival, graft function progressively declines, and many recipients return to insulin dependence within a few years posttransplant. The progressive loss of ß-cell function in islet transplants seems unlikely to be explained by allo- and autoimmune-mediated mechanisms alone and in a number of ways resembles ß-cell failure in type 2 diabetes. That is, both following transplantation and in type 2 diabetes, islets exhibit decreased first-phase glucose-stimulated insulin secretion, impaired proinsulin processing, inflammation, formation of islet amyloid, signs of oxidative and endoplasmic reticulum stress, and ß-cell death. These similarities suggest common mechanisms may underlie loss of insulin production in both type 2 diabetes and islet transplantation and point to the potential for therapeutic approaches used in type 2 diabetes that target the ß-cell, such as incretin-based therapies, as adjuncts for immunosuppression in islet transplantation.